3.

HEMOPOIESIS: BLOOD FORMATION 12

INTRODUC TION ○ Thrombopoiesis - production of
o Formed elements of blood have relatively platelets
short life spans ○ Lymphopoiesis or
o On any given day, numerous blood cells die Lymphocytopoiesis - production
and the body has to continuously produce of lymphocytes
new ones to maintain their numbers.
PRODUCTION SITES OF BLOOD ELEMENTS
● In utero, blood cells are produced:
TABLE OF CONTENTS
○ Initially, in mesoderm of yolk sac
1. Hematopoiesis
○ Later, liver and spleen
a. Production sites of blood
○ by second month of intrauterine
vessels
life
2. Hemopoietic Tissue
■ some long bones start to
a. Myeloid Tissue
ossify
b. Lymphoid Tissue
■ bone marrow becomes a
3. Origin of Formed Elements of Blood
site for blood cell formation
a. Pluripotential stem cells
● Subsequently, as more and more bones
b. Progenitor cells
ossify, the blood- cell forming activity of
4. Hematopoiesis
the liver and spleen decreases
a. Production sites of blood
● Postnatally, blood cells are produced:
vessels
○ exclusively in bone marrow
5. Hemopoietic Growth Factors
except for lymphopoiesis, which
6. Myeloid Stem Cells
also occurs in all lymphoid tissues
a. Erythropoiesis
and organs.
b. Granulopoiesis
c. Thrombopoiesis
HEMOPOIETIC TISSUE
d. Monopoiesis
● site of hemopoiesis
7. Lymphopopoiesis
○ formed elements develop from
a. Lymphopoiesis in Central
primitive cells (stem cells) to
Lymphoid Organs
mature forms
b. Lymphopoiesis in Peripheral
● Two Forms/ Kinds of Hemopoietic Tissue
Lymphoid Organs
○ Myeloid Tissue
○ Lymphoid Tissue

MYELOID TISSUE
HEMOPOIESIS (HEMATOPOIESIS)
● process of producing formed elements of
blood
● number of formed elements produced/day
(in adults):
○ 200 billion red blood cells
○ 10 billion neutrophils
● Hemopoiesis encompasses:
○ Erythropoiesis or
Erythrocytopoiesis - production
of red blood cells
○ Granulopoiesis or
Granulocytopoiesis - production
of granulocytes
○ Monopoiesis or Monocytopoiesis
- production of monocytes Figure 1. Myeloid tissue

1
TRANSCRIBERS: Frontliners, Group 3A
SUBTRANSHEAD: Ca rl Abellar
 ● site of hemopoiesis (all formed elements
of blood, including lymphocytes are
produced)
● Postnatally, synonymous with red bone
marrow
● In new borns, all the cavities in practically
all the bones in the body are filled with red
bone marrow.
● But as the bones increases in size, adipose
tissue invades most cavities of the bones.
● Red bone marrow in these cavities
becomes yellow bone marrow and
ceases to be a site for hemopoiesis.
● In adults, red bone marrow is confined to
spongy portion of flat bones,
○ notably sternum and ilium,
vertebral bodies, and the upper part
of the humerus and femur
Figure 2. Stroma
● Stroma (connective tissue framework)
○ composed of reticular fibers and
reticular cells
○ serves as framework for marrow
spaces (a complicated network of
interconnecting spaces called
marrow cavities) supplied with
numerous sinusoids (sinusoida l
capillaries)
● Parenchyma (functional component of a
tissue or organ)
○ blood cells in varying stages of
development
○ Adipose cells
○ Sinusoids – strews red bone marrow
and are lined by endothelium (thin
endothelial cells that rest on a
discontinuous basal lamina)
○ Endothelial Cells
TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
■ form lining epithelium
○ Perisinusoidal Macrophages
■ external to endothelial cells
■ Responsible for removing
foreign particulate material
and worn-out red blood cells
from the blood and marrow
cavities through
phagocytosis (phagocytose
with the help of processes
that extend into lumen of the
sinusoids)
Note: Newly matured blood cells reach sinusoids
by transcellular migration. When a mature
blood cell presses on the endothelial cell that lines
a bone marrow sinusoid, the endothelial cell
membrane responds by forming a temporary
opening, called migration pore, which closes
after the blood cell reaches the lumen of the
sinusoid.
LYMPHOID TISSUE
● site of lymphopoiesis
● only lymphocytes are produced
ORIGINS OF FORMED ELEMENTS OF BLOOD
Figure 3. Development of a zygote to a
blastocyst
o Totipotential stem cell- can multiply
infinitely
o The cells called blastomeres that arise
during the first few days of embryonic
development form a spherical structure
referred to as morula.
o Blastomeres are likewise totipotent
stem cells and they start to differentiate
shortly after they are formed.
2
 PLURIPOTENTIAL STEM CELLS

● can differentiate into any cell type

● can renew their numbers infinitely
● True Pluripotent Cells start to decrease
dramatically after 4th day of intrauterine
life (when the embryo has turned into a
Figure 4. Schema showing the differentia tion
fluid- filled sphere called blastocyst)
of pluripotential cells into various
● True totipotent cells do not exist multipotent stem cells
anymore by the 4th day of intrauterine
life.
● Examples of multipotent stem cells are
● The blastocyst consists of 2 cell types: (1)
(1) mesenchymal cells, (2)neuron stem
trophoblast that encloses the wall of the
cells, (3) glial stem cells, and (4)
blastocyst, and (2) inner cell mass or hemopoietic stem cells
embryonic stem cells which form a
● MESENCHYMAL CELLS
cluster of cells on one pole of the blastocyst
○ ultimately give rise to:
and give rise to fetus.
■ connective tissue cells
● The inner cell mass is simply pluripote nt
● fibroblasts; reticular
and not totipotent since it can no longer cells; adipocytes
form a placenta or fetal membrane.
■ muscle cells
● Subsequent divisions of the cells of the
■ chondrocytes
inner cell mass give rise to more
■ osteocytes
pluripotent stem cells and in a matter of
● HEMOPOIETIC STEM CELLS
days, these stem cells further differentiate ○ Stem cells for all formed element s
to multipotent stem cells.
of blood
● Multipotent stem cells are still versatile-
○ Numerous in embryo; few in adults
they can transform into many, albeit finite,
○ Postnatally, present only in red
types of cells and replicate very fast. bone marrow
● Multipotent stem cells are plentiful in the ○ Appears in the yolk sac:
embryo and fetus but rare in adults where
■ as early as week 2 of
they are found (in scarce amounts) in most
embryonic life
organs of the body where they replace
○ Migrates to liver, then spleen and
dead or damaged cells. finally in bone marrow where they
● When stem cells differentiate (i.e.
settle permanently (areas where
transform to specialized cells):
hemopoietic stem cells settle
○ they take a series of commitment
provide the appropriat e
decisions
environment for their proliferation
○ they lose potential to produce some and differentiation)
cell types while retaining
○ In organs: they colonize and divide
differentiation potential for some
to:
lineages
■ renew their number
○ As cells become more
■ differentiate into
differentiated, they become progenitor cells (in
progressively more restricted in
response to hemopoietic
their lineage potential until
growth factors and
eventually, they become unipotent
hormones which control
or committed to the formation of a
hemopoiesis)
single cell type. ● NEURONAL STEM CELLS
○ Likewise, their capacity to multiply
○ ultimately give rise to:
progressively decreases.
■ different types of neurons
● OTHERS- GLIAL STEM CELLS

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
 o Multipotential
PROGENITOR CELLS o And/ or extensive proliferative
Figure 5. Schema showing how Pluripotentia l capacity

● Late Progenitor Cells

cells differentiate into Progenitor cells

Figure 7. Late progenitor cells of the
 Hemopoietic Stem Cells Give Rise to
myeloid stem cell lineage
PROGENITOR CELLS when it
differentiates.
● committed to differentiating into cells of ○ Usually unipotential
○ Limited proliferative capacity
certain hemopoietic lineages
○ committed to specific lineage
● Progenitor Cells:
○ differentiate into precursor cells of
○ Myeloid Stem Cell
○ B Stem Cell lineage
○ T Stem Cell  Stem cells and progenitor cells
o Look alike under LM;
○ DC Stem Cell
immunocytology and marrow
culture techniques distinguishes
Myeloid Stem Cell
● Committed to differentiate to other them
o Small, round cells
formed elements of the blood
o Nucleus
● Stays in the bone marrow
o Centrally located that
● Decreases in number with age
contains fine chromatin
● 0.2% of nucleated cells in bone marrow of
adults material
o 2 or more nucleoli
● Needed until you die
o Cytoplasm
T Stem Cell
o Scanty
● Committed to become T cell
o Basophilic
● Migrates to thymus
B Stem Cell
● Committed to become B cell
● Stays in bone marrow
DC Stem Cell
● Committed to become lymphoid related
dendritic cells

There are 2 kinds of progenitor cells: (1) early

progenitor cells, and (2) late progenitor cells
● Early Progenitor Cells
Figure 8. Precursor cells of the myeloid stem
cell lineage

Precursor cells
o earliest form of a lineage that can
be distinguished from cells of other
Figure 6. Early progenitor cells of the lineages under LM
myeloid stem cell lineage

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
 o When a late progenitor cell
differentiates, it gives rise to a
precursor cell.
Note:
 ‘Blast’ - precursor cell
HEMOPOIETIC GROWTH FACTORS
 Control proliferation and differentiation of
various cell lineages from earliest stem
cells to mature cells
 Many act synergistically on different cell
lineages
 Hormones
o Erythropoietin- produced mainly
by kidneys; partly by liver
- Glycoprotein hormone
- Principal regulator of RBC
production
- Promotes the differentiation
of the cells of the erythroid
lineage
- Influences the more
differentiated cells in the
lineage to increase their iron
uptake and hemoglobin
production
o Thrombopoietin- produced mainly
by liver; partly by kidneys
- Primary regulator
megakaryopoiesis and
platelet production
- Stimulates the production
and differentiation of the
cells in the megakaryocytic
lineage
- Profoundly influences the
development of other
hemopoietic stem cells
 Hormone-like Growth Factors
o Stem cell factor (SCF)- stimulates
the proliferation and subsequent
differentiation of the multipotent
stem cells
o Granulocyte colony- stimulating
factor (G-CSF)- stimulates the
production and subsequent
differentiation of the stem cells of
the neutrophilic lineage
o Granulocyte- macrophage
colony stimulating factor (GM-
CSF)- stimulates the production,
growth, and differentiation of the
cells of the basophilic and
eosinophilic lineages, but which also
has a similar effect on the cells of
the other lineages including the
erythroid, neutrophilic, and
monocytic lineages
o Monocyte Colony- Stimulating
factor (M- CSF)- stimulates
monopoiesis
o Etc.
o Produced within the bone marrow
by:
o Stromal cells (fibroblast s
and reticular cells)
o Monocytes
o Macrophages
o Endothelial cells
o Lymphocytes
MYELOID STEM CELLS
of
Figure 9. Myeloid stem cell lineage
 The myeloid stem cells retain their
capacity to divide to renew their numbers
throughout the individual’s lifetime.
 This capability to divide however
diminishes as the individual ages.
 In adults, myeloid stem cells comprise
about 0.2% of the total population of
nucleated cells in red bone marrow.
 A myeloid stem cell first differentiates into
Colony- Forming Unit Granulocyte
Erythroid, Macrophage ,
Megakaryocyte (CFU- GEMM) before
giving rise to any of t he following cells:
Burst Forming Unit- Erythroid (BFU-E),
Burst Forming Unit- Megakaryocyte
(BFU-MK), Colony- Forming Unit
Granulocyte Macrophage (CFU-GM),
Colony Forming Unit- Eosinophil (CFU-
Eo), Colony Forming Unit- Mast Cell
(CFU- Mast).

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
  Early progenitor cells: CFU- GEMM, BFU- ○ hemoglobin increases and as a
E, BFU-MK, and CFU-GM result, c ytoplasmic acidophilia
 Late progenitor cells: CFU- Eo, CFU- Bas, increases
CFU- Mast
 BFU-E- committed to produce RBCs only,
but it still has extensive proliferative
capacity.
 Upon differentiation of its progenies, each
of them becomes a Colony Forming Unit-
Erythroid (CFU-E), a late progenitor
cell that has limited proliferative capacity.
 A Burst-Forming Unit- Megakaryocyte
(BFU- MK) still has extensive proliferative
capacity, but is committed to becoming a
megakaryocyte.
 When it differentiates, it becomes a
Colony- Forming Unit-Megakaryocy te
(CFU-MK), which like all late progenitor
cells, has limited proliferative capacity.
 A Colony- Forming Unit- Granulocyte
Macrophage (CFU-GM) is still a Figure 10. Cells of the erythroid lineage
multipotent cell that can give rise to two
*Refer to Table 2 for the description of the
late progenitor cells of the WBC lineages:
cells of the erythroid lineage.
Colony Forming Unit- Granulocyte
(CFU-G) that is destined to produce GRANULOPOIESIS
neutrophils, or Colony Forming Unit-
Monocyte/ Dendritic Cell (CFU-M/DC)
that is destined to produce either
monocytes or myeloid- related
dendritic cells.
 CFU- GM is probably the stem cell for
osteoclasts.
 The Colony- Forming Unit- Eosinophil
(CFU-Eo), Colony Forming Unit-
Basophil (CFU-Bas) and Colony
Forming Unit- Mast Cell (CFU-Mast) are
committed to produce eosinophils,
basophils, and mast cells, respectively.
Figure 11. Cells of the granulocytic lineage
ERYTHROPOIESIS
● Erythropoietin  In routine bone marrow smears, the
○ chief regulator of erythropoiesis neutrophilic, eosinophilic, and
● Proerythroblasts and Basophilic basophilic myeloblasts look alike despite
erythroblasts- capable of mitosis (3- 5 arising from different progenitor cells.
cell divisions) Nevertheless, one can distinguish them
● As cells mature in the stages inside the from the precursor cells of the other
bracket: cell lineages. This holds true for
○ decreases in size neutrophilic, eosinophilic, and
○ nucleus shrinks till pyknotic after basophilic promyelocytes as well.
which it is extruded  It takes about 11 days for a neutrophilic
○ ribosomes decrease resulting to myeloblast to transform into a
decreased basophilia of the segmenter, undergoing 5 mitotic
cytoplasm divisions in the process.
*Refer to Tables 3,4, and 5 for the description of
the cells of the granulocytic lineage.

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
 THROMBOPOIESIS
Figure 12. Cells of the Megakaryocytic
Lineage
 Platelets are cytoplasmic fragments of
a giant cell in the bone marrow called
megakaryocyte.
A. Megakaryopoiesis
● development of the megakaryocyte
● thrombopoietin
○ hormone that serves as primary
regulator of megakaryopoiesis
○ produced by liver and also by
kidneys
 It takes about 10 days for a
megakaryoblast to transform into a
mature megakaryocyte
B. Platelet formation
○ fragmentation of megakaryocyte
Figure 13. Platelet ribbon in vessel lumen
○ platelet ribbon (proplatelets)
■ aka. pseudopodia
■ long cytoplasmic processes of
megakaryoc ytes whose formation in
TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
the bone marrow marks the
transformation of the
megakaryocytes into platelets
■ enter lumen of bone marrow
sinusoids where they fragment
into platelets that then join the
circulating blood.
■ portions of ribbon pinched-off
○ megakaryocyte enter sinusoids intact, then
migrate to pulmonary vessels and
fragments
○ a megakaryocyte produces 4,000 – 8,000
platelets after which it presumably
degenerates.
* Refer to Table 6 for the description of the
cells of the megakaryocytic lineage
MONOPOIESIS
Figure 14. Cells of the monocytic lineage
 Differentiation of monoblasts into
monocytes takes about 55 hours.
*Refer to Table 7 for the description of the
cells of the monocytic lineage
LYMPHOPOIESIS
 Lymphoiesis occurs in various lymphoid
tissue and lymphoid organs.
 These tissues and organs are divided into
two groups:
o Central lymphoid organs-
thymus and bone marrow
o Peripheral lymphoid tissues and
organs
 lymph nodes
 spleen
 bone marrow
 Mucous associated lymphoid
tissue (MALT)
7
 tonsils
non-encapsulated
lymphoid tissues in
respiratory(i.e.
BALT), digestive (i.e.
GALT) and
genitourinary tracts
o lymph nodes, spleen, and mucosa-
associated lymphoid tissues (MALT
which inclues the tonsils and the
nonencapsulated lymphoid tissues
in the gastrointestinal (i.e. GALT),
respiratory (i.e. BALT) and
genitourinary tracts) Figure 16. Schema showing the cells involved
in the lymphocytic lineage which results in
LYMPHOPOIESIS IN CENTRAL LYMPHOID the formation of mature, immunocompete nt
ORGANS lymphocytes in the central lymphoid organs.

 In the thymus, the T- stem cells

differentiate into T- lymphoblasts (the
precursor cells of the lineage) and
proliferate.
 The B- stem cells start to differentiate in
the bone marrow when they receive the
appropriate signals in the form of growth
factors.
o B-stem cells undergo two
intermediate stages (Pro B- cell
and Pre- B cell) before they
become B- lymphoblasts,
precursor cells of this lineage.
 Lymphoblasts differentiate into
prolymphocytes after becoming mature
lymphocytes
Figure 15. Schema showing the precursor  Mature lymphocytes (i.e., B-cell and T-
cells of the progenitor cells of lymphocytes cell) leave the central lymphoid organs by
with emphasis in the role of central lymphoid entering blood and lymphatic vessels.
organs in the proliferation and maturation of  B cells and T cells released by thymus and
the progenitor cells of lymphocytes, i.e. T bone marrow
stem cells and B- cells, into mature and o mature
immunocompetent lymphocytes o immunocompetent
o small lymphocytes
 Upon differentiation from hemopoietic o naive (i.e., have not encountered
stem cells in the bone marrow, T - stem antigen yet)
cells migrate to thymus while B- stem cells o have mitotic capability
stays in the myeloid tissue (i.e., bone
marrow) LYMPHOPOIESIS IN PERIPHERAL
 Hemopoietic stem cells abound in the bone LYMPHOID ORGANS
marrow of embryos and fetuses.
 However, their numbers diminish rapidly
with age such that in adults, relatively few
still exist.
 Nevertheless, the bone marrow remains
a source of T- stem cells and B- stem Figure 17. Schema showing how
cells throughout life. lymphocytes move back and forth between

8
TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
the lymphoid organs and tissues and blood or
lymph, comprising a “re-circulating pool.
 Mature lymphocytes would then migrate
to, and take up residence in, the various
peripheral lymphoid tissues and
organs.
 In LM, B- lymphoblast and T - lymphoblast s
look alike. The same holds true for B-
prolymphocytes and T - prolymphocytes.
Note: Transformation of a cell from one
stage to the next is a very gradua l
process. Oftentimes, changes in the
cytoplasm do not go hand in hand with
changes in the nucleus. Accordingly, the
number of possible morphologic
gradations between stages is infinite.

Figure 18. Schema showing the various

functional type of lymphocytes

 Upon settling in the peripheral lymphoid

organs, B- cells and T- cells are small
lymphocytes that retain their mitotic
capability.
 This capability is aroused upon activation
in the presence of an antigen.
 Activation makes lymphocytes bigger.
Thereafter they divide extensively before
differentiating into various functional type
of lymphocytes.
 Some activated lymphocytes leave the
area of antigen exposure and enter the
bloodstream after which they seed other
peripheral lymphoid tissues and organs.
 They shuttle bac k and forth between the
different lymphoid tissues and organs by
joining the blood or lymph to comprise a
recirculating pool.
 T- cells recirculate more than B- cells

NK cells
● exact origin remains unknown
● probably originate from bone marrow
● do not arise from B or T cells
● do not get processed in thymus

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
Table 1. Progenitor and Precursor Cells of the Different Blood Cell Lineages

Cell Lineage Progenitor Cell Precursor Cell

Erythroid CFU- E proerythroblast

Granulocytic

 Neutrophilic CFU- G Neutrophilic myeloblast

 Eosinophilic
 Basophilic CFU-Eo Eosinophilic myeloblast

CFU- Bas Basophilic myeloblast

Megakaryocytic CFU- MK Megakaryoblast

Monocytic CFU- M/DC monoblast

Lymphocytic

 T-cell T stem cell T- lymphoblast

 B-cell
B stem cell B- lymphoblast

Table 2. Erythroid Lineage

Erythrocytic precursors Nucleus Cytoplasm Picture

Proerythroblast  spherical  scanty

 centrally located  basophilic; no
 a.k.a. pronormoblast  80% of cell hemoglobin
 precursor cell; earliest to  fine chromatin granules  organelles
be distinguished  1-2 nucleoli (mitochondria, Golgi
morphologically complex, centrioles and
 size: large cell, 22-28 abundant ribosomes ) in
um pale area around
 does not contain nucleus (perinuclear
hemoglobin yet halo)

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
 Basophilic erythroblast  spherical  intensely basophilic; but
 75% of cell with hemoglobin
 a.k.a: basophilic  coarse chromatin  often more basophilic
normoblast; early arranged in clock-face than the nucleus
normoblast pattern  EM shows well
 size: 16-18 um  nucleoli sometimes seen developed Golgi
 already synthesizes complex; numerous
hemoglobin polyribosomes,
mitochondria, and the
presence of
microtubules and
microfilaments.

Polychromatophilic  50% of cell  significant amount of

erythroblast  coarse, checkerboa rd hemoglobin
chromatin  grayish pink
 a.k.a:  no nucleolus  EM – few organelles.
polychromatophilic
normoblast;
intermediate normoblast
 size: 12-15 um

Normoblast  eccentric  contains a considerable

 pyknotic (chromat in amount of
 a.k.a: orthochromatic material is highly hemoglobin; thus, it is
erythroblast; late condensed) already pinkish, in
normoblast  less than 25% of cell routinely stained smears
 size: 9-11 um  acidophilic
 EM- paucity of
organelles
(mitochondria and Golgi
degenerating, and few
ribosomes)

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
 Reticulocyte ○ no nucleus  cytoplasm still with
centrioles; remnants of
 a.k.a. Golgi complex; some
polychromatophilic mitochondria &
erythrocyte ribosomes and has
 still synthesizes bluish tinge (due to
hemoglobin (The remaining
hemoglobin that a cytoplasmic
reticulocyte still needs to organelles)
synthesize could be as
much as 20% of what it
should have as a mature
RBC)
 0.8% of RBCs in blood-
it is not unusual for a
few reticulocytes to
prematurely enter
blood where they
complete their
maturation in about 24
to 28 hours)
 larger (about 9 um)
than RBC

Red blood cell

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
Table 3. Cells of the Neutrophilic lineage

Neutrophilic precursors Nucleus Cytoplasm Picture

Myeloblast  oval or round  scanty
● precursor cells  fine, evenly  moderately
● with limited mitotic distributed basophilic
capability chromatin  no granules
● can be granules, small  In EM- many
distinguished from clumps maybe seen mitochondria,
precursor cells of  one to three ribosomes, well-
other series but not nucleoli. developed rER
from each other
● large round cell
(15-20 um), but
smaller than
proerythroblast
(22-28 um)

Promyelocyte o Round or oval o more basophilic

o clumped than myeloblast
o Can’t be chromatin; thus, o contains
distinguished from the nucleolus is nonspecific,
each other often not visible azurophilic
morphologically granules (primary
o Larger (up to 25 um) granules) which
than myeloblast (15 - are not yet present
20 um) in the myeloblast
o Capable of mitosis o EM- membrane -
like bound cytoplasmic
granules and well-
developed rER.

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
 N. myelocyte o oval o more abundant
o chromatin than promyelocyte
o can be material coarse o less basophilic
distinguished from that forms clumps
basophilic and o nucleolus not visible specific granules
eosinophilic
myelocytes and the o little affinity for
same holds true for stains and too small
the progenies of to be appreciated
this cell. under LM.
o already has specific o Impart a lilac hue
cytoplasmic o initially near
(secondary) nucleus then
granules- serves as spreads to
a “marker” that the periphery
promyelocyte has o EM- less dense
differentiated to a than nonspecific
myelocyte granules
o slightly smaller o contain enzymes
than promyelocyte and proteins
o can still mitose (up collectively called
to 3 cell divisions phagocytins
before differentiating (bactericidal)
into neutrophilic nonspecific (azurophilic )
metamyelocytes) granules

o contain lysosomal
enzymes.

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
 N. metamyelocyte o deeply indente d o slightly basophilic
to one side o numerous specific
o about size of mature o chromatin consists granules
neutrophil (10-12 of coarse, dark outnumbering
um, in smears) clumps azurophilic
o no longer capable granules and
of mitosis almost equal to that
of the normal
mature
complement.

Stab cell (band form) o U- or S- shaped or o pale violet

elongated and o specific granules
o only in neutrophilic slightly curved equal to that of the
series that allows it to be full (mature)
o normally constitute distinguished from complement.
2-8 % of neutrophils N. metamyleocyte
in blood o Formation of lobes
in the nucleus marks
its transformation
into a mature
neutrophil or
segmenter.

Neutrophil aka.
segmenter

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
Table 4. Cells of the eosinophilic lineage

Eosinophil precursors Nucleus Cytoplasm Picture

Myelocyte  Chromatin material  Slightly basophilic
forms coarse clumps  Presence of
 first cell in the lineage
Azurophilic granules
that is morphologically
 Presence of Specific
distinguishable under
cytoplasmic
routine smears.
granules- distinguishes
eosinophilic myelocyte
from myelocytes of the
other granulocytic
lineages which can be
characterized as being
acidophilic and much
larger than those in a
neutrophilic
myelocyte

Metamyelocyte  Looks like its

neutrophilic counterpart
except for its
distinctive specific
cytoplasmic granules

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
Table 5. Cells of the Basophilic lineage

Basophil precursors Picture

Cytoplasm

Myelocyte  Looks like its neutrophilic and eosinophilic counterparts

except for their specific cytoplasmic granules and their
nucleus that stains less intensely and has fine r
chromatin granules
 Specific cytoplasmic granules
- Have a high affinity for basic dyes
- Blue or dark purple in routinely-stained
smears
- Larger, fewer, and of variable sizes
compared with those in their eosinophilic
counterparts

Metamyelocyte NOTE: There is no band form in the eosinophilic and

basophilic lineage. The metamyelocyte directly differentiates
into a mature eosinophil or basophil.

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
Table 6. Cells of the Megakaryocytic lineage

Platelet precursors Nucleus Cytoplasm Picture

Megakaryoblast o large o homogenous

o ovoid o intensely basophilic
o large cell (15-50 um) o slightly indented (numerous
o precursor cell of the o loose chromatin ribosomes)
megakaryocytic lineage o multiple nucleoli o EM: many
o undergoes a series (up however, not mitochondria; well-
to 7) of incomplete prominent developed rER and
type of mitosis called Golgi complex.
endomitosis, upon
which the cytoplasmic
elements duplicate
and at the end of the
division process, it forms
a promegakaryocyte .
No cytoplasmic
division occurs and
the daughter nucle i
remains fused.

Promegakaryocyte o several lobes o fine azurophilic

granules
o described by some o several pairs of
authors centrioles.
o results from
endomitosis of
megakaryoblast
(incomplete mitosis )
= forms multilobe d
nucleus
o 30-50 um

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
 Megakaryocyte o multilobulated o abundant
o coarse chromatin o basophilic, but less
o giant cell (50 -150 um) o indistinct nucleoli than
megakaryoblast
o numerous fine
nonspecific,
azurophilic granules
o EM: many ribosomes;
few ER and Golgi
complexes, many
membrane- bound
granules, and
numerous smooth-
surfaced membranes
tend to flatten.

Table 7. Monocytic lineage

Monocyte precursors Nucleus Cytoplasm

Monoblast  Oval or round  Scanty

 Fine chromatin granules  Moderately basophilic
o precursor cells of the
that are evenly dispersed  EM- free ribosomes,
monopoietic lineage
 Presence of few small polyribosomes, rER, a few
o large round cell (15- 20
clumps of chromatin mitochondria
um in diameter)
o virtually identical with
myeloblast (precursor
cells of the granulocytic
lineage) in LM
o can be distinguished from
myeloblast when nucleus
begin to indent &
azurophilic granule s
appear (which in
granulocytic series begins
to appear in the
promyelocytic stage
and its progenies).

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
 Promonocyte o large o basophilic but paler than
o indented monoblasts
o larger than monoblasts o paler than monoblast s o many azurophilic
o divides twice before its because of its finer granules.
progenies differentiate chromatin granules
into mature monocytes, o nucleoli often visible
after which monocytes
enter blood immediately.
Staying in the blood for a
short while, monocytes
migrate into connective
tissues where they
transform into
macrophages.

Table 8. Cells of the lymphocytic lineage

Lymphocyte precursors Nucleus Cytoplasm Picture

Lymphoblast o large o relatively abundant

o spherical basophilic cytoplasm
o large cell (> 25 um o one or 2 nucleoli o no azurophilic granules
diameter) o fine and highly dispersed
o normally, in thymus or chromatin material
bone marrow; not o Nucleus to cytoplasm
present in blood ratio: 4:1

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
 Prolymphocyte o chromatin condensed; o basophilic
this making the nucleoli o with azurophilic
o slightly smaller than not visible in most cases. granules
lymphoblast

==========================================
References:
1. PPT
2. Book

3.

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales
==========================================
PAST EXAMINATION A. myeloblast
B. myelocyte
2019 C. promyelocyte
1. In adults, hemopoiesis occurs in the: D. none of the above
A. Liver
B. Spleen 8. Stage of development during which the
C. Bone marrow nonspecific or azurophilic granules of the
D. All of the above granulocytes appear:
A. myeloblast
2. Reticular cells and reticular fibers form the B. myelocyte
stroma of: C. promyelocyte
A. Myeloid tissue D. metamyelocyte
B. Lymphoid tissue, except that in the thymus
C. Both 9. Stage of development during which the three
D. Neither types of lymphocytes can be distinguished
from each other under the light microscope:
3. Hemopoietic stem cells differentiate from the A. lymphoblast
cells of which part of the blastocyst? B. prolymphocyte
A. Trophoblast C. mature lymphocyte
B. Inner cell mass D. none of the above
C. Both
D. Neither 10. Cell which undergoes an incomplete type of
meiosis called endomitosis:
4. Colony Forming Units-Granulocyte (CFU-G) can A. myeloblast
ultimately give rise to: B. monoblast
A. neutrophils C. megakaryoblast
B. basophils D. lymphoblast
C. eosinophils
D. any of the above 11. Cells which are NOT present in normal blood:
A. lymphoblasts
5. Which is the largest of the following cells: B. stab cells
A. normoblast C. myeloblasts
B. basophilic erythroblast D. A & C above
C. polychromatophilic erythroblast
D. reticulocyte- 12. TRUE of the lymphocytes:
A. The B-stem cells and T-stem cells arise in
6. Which of the following cells has NO nucleus: the bone marrow.
A. normoblast B. The B-stem cells and T-stem cells
B. reticulocyte proliferate, mature and become
C. polychromatophilic erythroblast immunocompetent in the
D. A & B above peripherallymphoid tissues and organs.
C. Mature B cells and T cells are incapable of
7. Stage of development during which the three mitosis
types of granulocytes can be distinguished D. All of the above
from each other:

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TOPIC: 3. Blood Formation
LECTURER: Dr. Ed Gonzales